This invention relates to a process for the preparation of 7,8-epoxy-2-methyloctadecane, the cis-isomer of which is the essential component of the sex pheromone of the gypsy moth Porthetria dispar.
As is known, pheromones are substances which serve in general to stimulate chemically mediated behavioral interactions of organisms with one another, in a narrower sense such interactions of insects with one another. Thus, among the pheromones are counted primarily sex attractants, as well as substances causing the expression of alarm, aggregation, attack, defense, etc., of the insects; these pheromones are generally effective even in minute quantities. By the use of refined analysis and synthesis methods, numerous pheromones have been isolated in recent years, explained with regard to their constitution and in part even synthesized. Among these pheromones is cis-7,8-epoxy-2-methyloctadecane, the sex attractant of the gypsy moth, which is also known under the name of disparlure; see D. A. Bierl et al., Science 170:87 (1970).
The sex pheromones are of considerable practical interest inasmuch as it is possible with their aid to selectively combat individual, damaging types of insects. The procedure followed is to attract individual insects of the type to be combated with the aid of the sex pheromone and then to destroy the insects by means of insecticides or electric traps and/or to prevent the insects from reproducing by chemosterilization or radiosterilization. In this way, the populations of destructive types of insects can be reduced to a tolerable level without the danger of exerting an adverse effect on harmless or useful types of insects.
The gypsy moth is generally counted among the destructive insects. In the northeastern United States alone, the gypsy moth attacks about 200,000 hectares of forest each year, causing considerable expense and thus economic losses. See, for example, Chem. Eng. News 35 (Sept. 28, 1970); E. A. Cameron in "Pheromones," publishers M. C. Birch, North Holland Publishing Company, Amsterdam-London (1974): 431; and Chemical Week 28 (Oct. 23, 1974). The interest in inexpensive disparlure syntheses is, therefore, understandable.
However, most of the methods described in the literature have more or less severe deficiencies, primarily the number of synthesis steps which, in part, cause difficulties. Furthermore, considerable efforts must be expended in providing the starting materials necessary for the manufacture of larger quantities of disparlure.
The following processes have been described for preparing 2-methyl-7-octadecene, which is easily converted by epoxidation into 7,8-epoxy-2-methyloctadecane:
1. 1-Bromo-6-methylheptane, obtainable by adding hydrogen bromide to 6-methyl-1-heptene (an olefin not commercially available) is converted with triphenylphosphine into the quaternary phosphonium salt, and the ylide obtainable therefrom is reacted with undecanal into a mixture of cis- and trans-2-methyl-7-octadecene, e.g. see B. A. Bierl et al., Science 170:87 (1970).
2. 1-Bromodecane is reacted with sodium acetylide in tetrahydrofuran/dimethylformamide to 1-dodecine which, after metallizing with butyllithium, is alkylated with isoheptyl bromide, obtained by a four-stage synthesis, to form 2-methyl-7-octadecene. Partial hydrogenation of the latter results in the cis-2-methyl-7-octadecene; see K. Eiter, "Angew. Chemie" [Applied Chemistry] 84 : 67 (1972); and DOS (German Unexamined Laid-Open Application) No. 2,145,454).
3. The process of C-chain extension of 1-dodecine with isoheptyl bromide, described under (2), was published by two other sources, with minor changes in the choice of the reaction conditions and the synthesis of the starting materials, e.g., see (B. G. Kovalev et al., Zh. Org. Kim. 9(1) : 6 [1973]; summarized in Chemical Abstracts 78 : 84127 (1973); A. A. Shamshurin et al., Khim. Prir. Soedin. 9(4) : 545 (1973); summarized in Chemical Abstracts 80 : 36927 (1974).
4. Isoamyl bromide is converted, after being subjected to a Grignard reaction with oxetane, into 6-methyl-1-heptanol from which 1-bromo-7-methylheptane can be obtained. The latter is converted into the corresponding phosphonium salt with triphenylphosphine. The ylide obtainable therefrom with potassium can be linked with undecanal to produce 2-methyl-cis-octadecene-(7); see H. J. Bestmann and O. Vostrowsky, Tetrahedron Lett. 207 (1974).
5. 4-Methylpentyl chloride is metallized with lithium and the thus-produced organometallic compound is reacted in situ with triphenylvinylsilane. Undecanal is then added dropwise to this reaction mixture; see T. H. Chan and E. Chang, J. Org. Chem. 39 : 3264 (1974).
6. A multistage process for the preparation of optically active disparlure has recently been published and is mentioned herein merely for the sake of completeness, see S. Marumo et al., J. Amer. Chem. Soc. 96 : 7842 (1974).
None of these multistage syntheses offers the possibility of producing the sex pheromone inexpensively on a large commercial scale.